Oxidation of branched-chain amino acids in skeletal muscle and liver of rat. Effects of octanoate and energy state.
The effect of octanoate on the oxidative decarboxylation of 14C-labeled amino acids has been studied in perfused hindquarter and liver of rat. Regulation of the branched-chain alpha-keto acid dehydrogenase has been further studied with alpha-[14C-1]ketoisovalerate in isolated rat muscle and liver mitochondria. (1) Octanoate has a stimulatory effect on the oxidation of branched-chain amino acids in perfused hindquarter. The oxidative decarboxylation of other amino acids are inhibited. Octanoate inhibits the oxidative decarboxylation of all amino acids in perfused liver. (2) The oxidation of valine is stimulated by octanoate and hexanoate also in isolated muscle mitochondria. The stimulatory effect is probably related to activation of the fatty acids since acyl-carnitines inhibit the oxidation. (3) The oxidation of alpha-ketoisovalerate in mitochondria is inhibited by competing substrates (pyruvate, alpha-ketoglutarate and succinate). This inhibition is counteracted by octanoate and ADP. (4) Low concentrations (1-5 microM) of 2,4-dinitrophenol (DNP) activates whereas higher concentrations inactivates the branched-chain alpha-keto acid dehydrogenase in intact but not in solubilized muscle mitochondria. The inactivation is counteracted by ATP, but is increased by octanoate. (5) The observations seem to suggest that the activation (like the inactivation) of branched-chain alpha-keto acid dehydrogenase in skeletal muscle is dependent on the mitochondrial energy state which therefore may regulate both activation and inactivation of the dehydrogenase.
D019297:2,4-Dinitrophenol; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000597:Amino Acids, Branched-Chain / Q000378:metabolism*; D000818:Animals; D002210:Caprylates / Q000494:pharmacology*; D002245:Carbon Dioxide / Q000378:metabolism; D002331:Carnitine / Q000031:analogs & derivatives / Q000494:pharmacology; D004140:Dinitrophenols / Q000494:pharmacology; D005227:Fatty Acids / Q000494:pharmacology; D005260:Female; D045782:Hemiterpenes; D007651:Keto Acids / Q000378:metabolism; D007658:Ketone Oxidoreductases / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000378:metabolism*; D008931:Mitochondria, Muscle / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D013379:Substrate Specificity
D000597:Amino Acids, Branched-Chain; D002210:Caprylates; D004140:Dinitrophenols; D005227:Fatty Acids; D045782:Hemiterpenes; D007651:Keto Acids; D009097:Multienzyme Complexes; D002245:Carbon Dioxide; D000244:Adenosine Diphosphate; C001505:alpha-ketoisovalerate; D000255:Adenosine Triphosphate; D007658:Ketone Oxidoreductases; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D019297:2,4-Dinitrophenol; D002331:Carnitine